Fig. 2

Pathophysiology of AMS and HACE. There are three interconnected mechanisms involved in HACE progression under altitude hypoxia: a cerebral hemodynamic imbalance due to disrupted arterial inflow and venous outflow, driven by neurovascular unit dysfunction, elevated [H⁺], vasoactive mediators, and HIF-1α-mediated VEGF upregulation, leading to increased CBV and microvascular hyperperfusion; b neurohormonal and inflammatory responses involving ROS, proinflammatory cytokines (e.g., CRP, IL-6, TNF-α), and neurotransmitter alterations, which induce endothelial cell injury, tight junction disruption, and BBB breakdown, resulting in vasogenic edema; and c the cytotoxic edema cascade initiated by impaired Na⁺/K⁺-ATPase due to reduced ATP synthesis, causing intracellular Na⁺ and water accumulation